The present invention relates to novel benzimidazoles, their preparation and their use as inhibitors of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30) for the preparation of drugs.
Poly(ADP-ribose)polymerase (PARP) or, as it is also known, poly(ADP-ribose)synthase (PARS) is a regulatory enzyme which is found in cell nuclei (K. Ikai et al., J. Histochem. Cytochem. 31 (1983), 1261-1264). It is assumed that PARP plays a role in repairing DNA breaks (M. S. Satoh et al., Nature 356 (1992), 356-358). Damage to or breaks in the DNA strands activate the enzyme PARP which, if it has been activated, catalyses the transfer of ADP-ribose from NAD (S. Shaw, Adv. Radiat.Biol. 11 (1984), 1-69). Nicotinamide is liberated from NAD. Nicotinamide is converted back into NAD with consumption of the energy carrier ATP by other enzymes. Overactivation of PARP would accordingly result in an unphysiologically high consumption of ATP, and this leads to cell damage and cell death in extreme cases.
It is known that radicals such as the superoxide anion, NO and hydrogen peroxide can lead to DNA damage in cells and hence activate PARP. The formation of large amounts of radicals is observed in a number of pathophysiological conditions, and it is assumed that this accumulation of radicals leads or contributes to the observed cell or organ damage. These include, for example, ischemic conditions of organs, as in stroke, myocardial infarct (C. Thiemermann et al., Proc. Natl. Acad. Sci. USA 94 (1997), 679-683) or ischemia of the kidneys, as well as reperfusion damage as occurs, for example, following the lysis of myocardial infarct (see above: C. Thiemermann et al.). The inhibition of the enzyme PARP might accordingly be a means for preventing or reducing this damage at least in part. PARP inhibitors might therefore constitute a new therapeutic principle for treating a number of disorders.
The enzyme PARP influences the repair of DNA damage and could thus also play a role in therapy of cancer diseases, since the higher action potential against tumor tissue was observed in combination with cytostatic substances (G. Chen et al. Cancer Chemo. Pharmacol. 22 (1988), 303).
Nonlimiting examples of tumors are leukemia, glioblastomas, lymphomas, melanomas, carcinomas of the breast and cervical carcinomas.
It was also found that PARP inhibitors can have an immunosuppressive effect (D. Weltin et al. Int. J. Immunopharmacol. 17 (1995), 265-271).
It was also discovered that PARP is involved in immunological diseases or disorders in which the immune system plays an important role, for example rheumatoid arthritis and septic shock, and that PARP inhibitors can have an advantageous effect on the course of the disorder (H. Krxc3x6ger et al. Inflammation 20 (1996), 203-215; W. Ehrlich et al. Rheumatol. Int. 15 (1995), 171-172; C. Szabo et al., Proc. Natl. Acad. Sci. USA 95 (1998), 3867-3872; S. Cuzzocrea et al. Eur. J. Pharmacol. 342 (1998), 67-76).
For the purposes of this invention, PARP is also understood as meaning isoenzymes of the PARP enzyme described above.
Furthermore, the PARP inhibitor 3-aminobenzamide exhibited protective effects in a model for circulatory shock (S. Cuzzocrea et al., Br. J. Pharmacol. 121 (1997), 1065-1074).
PARP is also involved in diabetes mellitus (V. Burkhart et al., Nature Medicine (1999), 5314-19).
Benzimidazoles have been widely described.
The synthesis of 2-phenylbenzimidaz-4-ylamides which also carry a substituted alkyl chain on the amide radical and which are said to have a cytotoxic effect is mentioned in J. Med. Chem. 33 (1990), 814-819. WO 97/04771 mentions 4-benzimidazolamides which inhibit PARS. In particular, derivatives which carry a phenyl ring in the 2-position, where the phenyl ring may furthermore be substituted by simple substituents such as nitro, methoxy or CF3, are described there as being effective. Although some of these substances exhibit good inhibition of the enzyme PARP, the derivatives described there have the disadvantage that they have little or no solubility in aqueous solutions and hence cannot be applied as an aqueous solution.
Benzimidazoles which carry a piperidine ring in the 2-position have also been described. Thus, in J. Het. Chem. 24 (1987), 31, derivatives have been prepared as antihistamine drugs. In J. Het. Chem. 32 (1995), 707 and J. Het. Chem. 26 (1989), 541, analogous compounds having the same use have been described. 2-Piperidinylbenzimidazoles are mentioned in EP 818454 as antihistamine drugs and in WO 9736554 as agents against hepatitis. Derivatives are likewise mentioned in CA 80, 146143, Fr. 2103639 and in Khim. Geterotsikl. Soedin 1 (1974), 104.
However, the importance of substituents on the phenylaromatics in the benzimidazole fragment has not been investigated. Furthermore, those benzimidazoles which carry a 4- to 8-membered heterocycle, in particular a piperidine ring, in the 2-position have not been described to date as being PARP inhibitors.
The present application describes the surprising finding that the introduction of a carboxamide radical on the benzimidazole aromatic gives benzimidazoles which constitute novel and highly effective PARP inhibitors, provided that they are substituted in the 2-position by a saturated heterocycle.
In a number of treatments, such as for stroke, the active compounds are applied intravenously as an infusion solution. For this purpose, it is necessary to have substances, in this case PARP inhibitors, which have sufficient water solubility at or about physiological pH (i.e. pH of 5-8), so that an infusion solution can be prepared. However, many of the PARP inhibitors described, in particular the more effective PARP inhibitors, have the disadvantage that they exhibit only little or no water solubility at the pH values and are therefore not suitable for intravenous application. Such active compounds can be applied only with excipients which are intended to impart water solubility (cf. WO 97/04771). These excipients, for example polyethylene glycol and dimethyl sulfoxide, frequently cause side effects or are even not tolerated. No highly effective PARP inhibitors having sufficient water solubility have been described to date.
It was surprisingly found that benzimidazoles which carry a piperidine ring on the imidazole ring are highly effective inhibitors and, owing to the incorporation of the aliphatic amine radical, permit salt formation with acids, resulting in substantially improved water solubility and hence permitting the preparation of an infusion solution.
The present invention describes novel benzimidazole derivatives of the formula I which have advantages over the compounds described above and constitute potent PARP inhibitors and at the same time have sufficient water solubility. When compounds of the formula I are referred to, they are understood as meaning the compounds of the formulae Ia and Ib. The present invention relates to substituted benzimidazoles of the formula I: 
where
R1 is hydrogen or branched or straight-chain C1-C6-alkyl, where one carbon atom of the alkyl radical may furthermore carry OR5 (where R5 is hydrogen or C1-C4-alkyl), or one carbon atom in the chain may also carry an xe2x95x90O group or a group NR8R9, where R8 and R9, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the carbon chains in R8 or R9 or the ring formed by NR8R9 may furthermore carry a radical R6 which, independently of R2, may have the same meaning as R2,
R4 is hydrogen, branched or straight-chain C1-C6-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR8R9, NHxe2x80x94COxe2x80x94R10 or OR8, where R8 and R9, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical (branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, COxe2x80x94R41, COOR41 or phenyl), and R10 may be hydrogen, C1-C4-alkyl or phenyl and R41 may have the same meanings as R21,
A is a saturated or monounsaturated heterocyclic 4- or 8-membered ring which contains one or two nitrogen atoms and, optionally, an oxygen or sulfur atom, which ring is substituted by R2 and R3, where
R2 is hydrogen, branched or straight-chain C1-C8-alkyl which may furthermore be substituted by R23, and a carbon atom of the chain may carry an xe2x95x90O group, C3-C7-cycloalkyl-C1-C4-alkyl, xe2x80x94COxe2x80x94(NH)0,1xe2x80x94R21, COOR21 or phenyl, where R21 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C3-C7-cycloalkyl or phenyl, and each radical may furthermore carry (CH2)0-2xe2x80x94R23 and the respective phenyl ring in turn may furthermore be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain C1-C4-alkyl, nitro, CF3, cyano, xe2x80x94(CH2)0-2xe2x80x94NR24R25, NHxe2x80x94COxe2x80x94R10, OR10, COOR10, SO2xe2x80x94C1-C4-alkyl, SO2Ph, SO2NH, NHSO2xe2x80x94C1-C4-alkyl, NHSO2Ph and CF3, where R24 and R25, independently of one another, are each hydrogen or C1-C4-alkyl and NR24R25 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, COxe2x80x94R22, COOR22 (where R22 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C3-C7-cycloalkyl or phenyl) or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and
R23 is NR26R27 where R26 and R27 are each hydrogen, C1-C6-alkyl, C0-C4-alkylphenyl, where the phenyl ring may furthermore be substituted by up to 3 radicals Cl, F, Br, I, C1-C4-alkyl, CF3, CN, SO2xe2x80x94C1-C4-alkyl, SO2-phenyl, NO2, NH2, NHCOxe2x80x94C1-C4-alkyl, NHCO-phenyl, OH, Oxe2x80x94C1-C4-alkyl, Oxe2x80x94C1-C4-alkylphenyl, and NR26R27 may also be a cyclic amine having 3 to 8 members, where a further hetero atom such as O, N and S may also additionally be present, and the ring may furthermore be substituted by a radical R28 where R28 may be C1-C4-alkyl and C1-C4-alkylphenyl,
R3 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl which is unsubstituted or substituted by C1-C6-alkyl or C3-C7-cycloalkyl which is unsubstituted or substituted by C1-C6-alkyl, where one carbon atom of the radical may furthermore carry a phenyl ring which in turn may also be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain C1-C4-alkyl, nitro, CF3, cyano, (CH2)0-2xe2x80x94NR32R33, NHxe2x80x94COxe2x80x94R10, OR10, COOR10, SO2xe2x80x94C1-C4-alkyl, SO2Ph, CH3, SO2NH, NHSO2xe2x80x94C1-C4-alkyl, NHSO2Ph and CF3, where R32 and R33, independently of one another, are each hydrogen or C1-C4-alkyl and NR32R33 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, COxe2x80x94R31, COOR31 or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and R31 may have the same meaning as R21,
and their tautomeric forms, possible enantiomeric and diastereomeric forms, their prodrugs and possible physiologically tolerated salts.
The compounds of the formula I where R1 is hydrogen are preferred.
The compounds of the formula I where R2 is hydrogen are preferred.
The compounds of the formula I where R4 is hydrogen are preferred.
The compounds of the formula I where R3 is bonded to the nitrogen of A are preferred.
The compounds of the formula I where R3 is hydrogen, C1-C6-alkyl, benzyl or phenethyl are preferred.
The compounds of the formula I where R1, R2 and R4 are each hydrogen and A is piperidine which is bonded at the 4-position on the benzimidazole and R3 is hydrogen, C1-C6-alkyl, benzyl or phenethyl and is bonded in the 1-position on the piperidine ring are particularly preferred.
The respective meanings of R5 to R10 are independent of one another in R1 to R4.
The preferred meanings of NR8R9, NR24R25 and NR32R33, as cyclic amine, are piperidine, pyrrolidine, piperazine and homopiperazine. In the case of piperazine and homopiperazine, the ring may preferably furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, COxe2x80x94R7 or phenyl.
The preferred meaning of A is piperidine, pyrrolidine, piperazine, morpholine or homopiperazine.
The compounds of the formula I where A is piperazine or piperidine are particularly preferred.
The compounds of the formula I may be used in the form of racemates, enantiomerically pure compounds or diastereomers. If enantiomerically pure compounds are desired, these can be obtained, for example, by carrying out a classical resolution of the racemate with the compounds of the formula I or their intermediates used in a suitable optically active base or acid.
The saturated or monounsaturated cyclic structures A may be present as cis-isomers, trans-isomers or mixtures thereof.
The present invention also relates to compounds which are mesomers or tautomers of compounds of the formula I.
The present invention furthermore relates to the physiologically tolerated salts of the compound I, which can be obtained by reacting compounds I with a suitable acid or base. Suitable acids and bases are listed, for example, in Fortschritte der Arzneimittelforschung, 1966, Birkhxc3xa4user Verlag, Vol. 10, pages 224-285. These include, for example, hydrochloric acid, citric acid, tartaric acid, lactic acid, phosphoric acid, methanesulfonic acid, acetic acid, formic acid, maleic acid, fumaric acid, etc., and sodium hydroxide, lithium hydroxide, potassium hydroxide and Tris.
Prodrugs are understood as meaning those compounds which are metabolized in vivo to give compounds of the formula I. Typical prodrugs are phosphates, carbamates of amino acids, esters and others.
The preparation of the novel benzimidazoles I can be carried out by various routes which are shown in synthesis scheme 1. 
The benzimidazole I or VII is obtained by condensation of the aldehyde V with phenylenediamines VI, the procedure preferably being carried out in polar solvents, such as ethanol or dimethylformamide, and with the addition of acids, such as acetic acid, at elevated temperatures, as a rule from 80 to 120xc2x0 C. It is advantageous for the reaction to add weak oxidizing agents, such as copper(II) salts, which are added as aqueous solution. 
If, in the benzimidazole VII, R is NH2, novel compounds I are formed directly in the condensation. Otherwise, if R is O-alkyl, these esters can be reacted with ammonia, if required at elevated temperatures and superatmospheric pressure, to give the amide I. Alternatively, the esters VII can be reacted with hydrazine in polar solvents, such as the alcohols butanol and ethanol or dimethylformamide, at elevated temperatures, preferably from 80 to 130xc2x0 C., the result being hydrazide VII (R=NHNH2) which can then be reduced under reductive conditions, for example with Raney nickel in alcohols under reflux, to give the amide I.
The radical R1 on the benzimidazole radical in I (R1=H) is introduced under conventional alkylating conditions. Benzimidazoles I are alkylated with R1xe2x80x94L, where L is a leaving group, using a base at from 25 to 150xc2x0 C., but mainly at elevated temperatures such as from 60 to 130xc2x0 C., the novel product I where R1xe2x89xa0hydrogen being obtained. The procedure is carried out in solvents, for example dimethylformamide, dimethylsulfoxide, alcohols, e.g. ethanol, ketones, e.g. methyl ethyl ketone or acetone, aliphatic ethers, e.g. tetrahydrofuran, and hydrocarbons, e.g. toluene, it also being possible to use mixtures. Suitable bases are, for example, alcoholates, e.g. sodium ethanolate and potassium tert-butanolate, carbonates, e.g. potassium carbonate, hydrides, e.g. sodium hydride, and hydroxides, e.g. sodium hydroxide and potassium hydroxide.
Various crown ethers, such as 18-crown-6, may also be added in catalytic amounts. Phase transfer conditions may also be employed (for methods, cf. R. C. Larock, Comprehensive Organic Transformations, 1989, page 445 et seq.). The leaving group L used may be a halide, e.g. bromide, chloride or iodide, or, for example, a tolysate or mesylate. 
Alternatively to the aldehydes V shown in Scheme 1 it is also possible to use benzoic acids, such as IX (cf. Scheme 2), or benzonitriles, such as XIII (cf. Scheme 3), instead of the benzaldehyde. The preparation of these derivatives is carried out analogously to the preparation of the substituted benzaldehydes V. Starting from IX, the condensation to give VII is carried out in two stages. First, the benzoic acid XI is reacted with the aniline VI with a peptide-like coupling to give the amide XII. The conditions used here are the conventional ones which are listed, for example, in Houben-weyl, Methoden der Organischen Chemie, 4th Edition, E5, Chapter V, or C. R. Larock, Comprehensive Organic Transformations, VCH Publisher, 1989, page 972 et seq. Cyclization to the benzimidazole is then effected at elevated temperatures, for example from 60 to 180xc2x0 C., with or without solvents, such as dimethylformamide, with the addition of acids, such as acetic acid, or directly in acetic acid itself.
The reaction of the phenylenediamine VI with a benzonitrile XIII is likewise effected under conventional conditions. It is possible to employ solvents, such as dimethylformamide, with the addition of acids at elevated temperatures, such as from 60 to 200xc2x0 C. However, it is also possible to use the conventional methods for the preparation of amides from benzonitriles, as described in J. Amer. Chem. Soc. (1957), 427 and J. Org. Chem. (1987), 1017.
The substituted benzimidazoles I contained in the present invention are inhibitors of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30).
The inhibitory effect of the substituted benzimidazoles I was determined by an enzyme test already known in the literature, the Ki value being determined as a measure of activity. The benzimidazoles I were measured in this way for an inhibitory effect of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30).
The substituted benzimidazoles of the formula I are inhibitors of poly(ADP-ribose)polymerase (PARP) or, as it is also referred to, poly(ADP-ribose)synthase (PARS) and can therefore be used for the treatment and prophylaxis of disorders which are associated with increased activity of these enzymes.
The compounds of the formula I can be used for preparing drugs for the treatment of damage following ischemias and for prophylaxis where ischemias of various organs are expected.
The present benzimidazoles of the formula I can then be used for the treatment and prophylaxis of neurodegenerative disorders which occur after ischemia, trauma (craniocerebral trauma), massive bleeding, subarachnoid hemorrhages and stroke, and of neurodegenerative disorders such as multi-infarct dementia, Alzheimer""s disease and Huntington""s disease and of epilepsies, in particular of generalized epileptic attacks, for example petit mal and tonoclonic attacks and partial epileptic attacks such as temporal lobe, and complex partial attacks, and furthermore for the treatment and prophylaxis of cardiac damage following myocardial ischemias and damage to the kidneys following renal ischemias, for example acute renal insufficiency, acute renal failure, damage which is caused by drug therapy such as, for example, during ciclosporin therapy or damage which occurs during or after a kidney transplantation. Furthermore, the compounds of the formula I can be used for the treatment of acute myocardial infarction and damage which occurs during and after its lysis under treatment with drugs (for example with TPA, reteplase or streptokinase or mechanically with a laser or Rotablator) and of microinfarcts such as, for example, during and after replacement of the heart valve, aneurysm resections and heart transplantations. The present benzimidazoles I can also be used for the treatment of a revascularization of critically narrowed coronary arteries, for example in PCTA and bypass operations, and critically narrowed peripheral arteries, for example arteries of the leg. Moreover, the benzimidazoles I may be useful in the chemotherapy of tumors and their metastasis and for the treatment of inflammations and rheumatic disorders, for example rheumatoid arthritis. In addition, the compounds of the formula I can be used to treat diabetes mellitus or to treat sepsis and multiorgan failure such as, for example, during septic shock and adult respiratory distress syndrome (ARDS, shock lung).
The novel drug formulations contain a therapeutically effective amount of the compounds I in addition to the conventional drug excipients.
For local external application, for example in the form of powders, ointments or sprays, the active compounds may be present in the conventional concentrations. As a rule, the active compounds are present in an amount of from 0.001 to 1, preferably from 0.001 to 0.1, % by weight.
In the case of internal use, the preparations are administered in single doses. From 0.1 to 100 mg per kg of body weight are administered in a single dose. The formulation can be administered daily in one or more doses, depending on the type and severity of the disorders.
Depending on the desired method of application, the novel drug formulations contain the conventional carriers and diluents in addition to the active compound. For local external application, pharmaceutical excipients such as ethanol, isopropanol, oxethylated castor oil, oxethylated hydrogenated castor oil, polyacrylic acid, polyethylene glycol, polyethylene glycol stearate, ethoxylated fatty alcohols, liquid paraffin, vaseline and lanolin, may be used. For internal use, for example, lactose, propylene glycol, ethanol, starch, talc and polyvinylpyrrolidone are suitable.
Antioxidants, such as tocopherol and butylated hydroxyanisole, and butylated hydroxytoluene, flavor-improving additives, stabilizers, emulsifiers and lubricants may furthermore be present.
The substances contained in the formulation in addition to the active compound, and the substances used in the preparation of pharmaceutical formulations, are toxicologically safe and are compatible with the respective active compound. The preparation of the drug formulations is carried out in a conventional manner, for example by mixing the active compound with other conventional carriers and diluents.
The drug formulations can be administered by various methods of application, for example perorally, parenterally, such as intravenously by infusion, subcutaneously, intraperitoneally and topically. Thus, the formulations such as tablets, emulsions, infusion and injection solutions, pastes, ointments, gels, creams, lotions, powders and sprays are possible.
In addition to the substances stated in the examples, the following compounds are particularly preferred and can be synthesized according to said preparation methods:
1. 2-(N-(O-tert-butoxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide
2. 2-(N-methylpiperidin-4-yl)benzimidazole-4-carboxamide
3. 2-(N-isopropylpiperidin-4-yl)benzimidazole-4-carboxamide
4. 2-(N-cyclohexylpiperidin-4-yl)benzimidazole-4-carboxamide
5. 2-(N-(trans-4-propylcyclohex-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
6. 2-(N-benzylpiperidin-4-yl)benzimidazole-4-carboxamide
7. 2-(N-(2-phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
8. 2-(N-(2(4-fluorophenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
9. 2-(N-(2(4-chlorophenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
10. 2-(N-(2(4-bromophenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
11. 2-(N-(2(4-iodophenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
12. 2-(N-(2(4-nitrophenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
13. 2-(N-(2(4-cyanophenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
14. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
15. 2-(N-(2(4-methylphenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
16. 2-(N-(2(4-hydroxyphenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
17. 2-(N-(2(4-methoxyphenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
18. 2-(N-(2(4-(Nxe2x80x2,Nxe2x80x2-dimethylamino)phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
19. 2-(N-(2(4-(Nxe2x80x2-acetylamino)phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
20. 2-(N-(2(4-(Nxe2x80x2-phenylsulfonylamino)phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
21. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
22. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
23. 2-(N-acetylpiperidin-3-yl)benzimidazole-4-carboxamide
24. 2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
25. 2-(N-isopropylpiperidin-3-yl)benzimidazole-4-carboxamide
26. 2-(N-cyclohexylpiperidin-3-yl)benzimidazole-4-carboxamide
27. 2-(N-(trans-4-propylcyclohex-1-yl)piperidin-3-yl)benzimidazole-4-carboxamide
28. 2-(N-(2-phenyl)eth-1-yl)piperidin-3-yl)benzimidazole-4-carboxamide
29. 2-(N-(2(4-chlorophenyl)eth-1-yl)piperidin-3-yl)benzimidazole-4-carboxamide
30. 2-pyrrolidin-3-ylbenzimidazole-4-carboxamide
31. 2-(N-acetylpyrrolidin-3-yl)benzimidazole-4-carboxamide
32. 2-(N(O-tert-butoxycarbonyl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
33. 2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
34. 2-(N-isopropylpyrrolidin-3-yl)benzimidazole-4-carboxamide
35. 2-(N-cyclohexylpyrrolidin-3-yl)benzimidazole-4-carboxamide
36. 2-(N-(trans-4-propylcyclohex-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
37. 2-(N-benzylpyrrolidin-3-yl)benzimidazole-4-carboxamide
38. 2-(N-(2-phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
39. 2-(N-(2(4-chlorophenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
40. 2-(N-(2(4-nitrophenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
41. 2-(N-(2(4-cyanophenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
42. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
43. 2-(N-(2(4-methylphenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
44. 2-(N-(2(4-hydroxyphenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
45. 2-(N-(2(4-methoxyphenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
46. 2-(N-(2(4-(Nxe2x80x2,Nxe2x80x2-dimethylamino)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
47. 2-(N-(2(4-(Nxe2x80x2-acetylamino)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
48. 2-(N-(2(4-(Nxe2x80x2-phenylsulfonylamino)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
49. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
50. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
51. 2-pyrrolidin-2-ylbenzimidazole-4-carboxamide
52. 2-(N-acetylpiperazin-4-yl)benzimidazole-4-carboxamide
53. 2-(N(O-tert-butoxycarbonyl)piperazin-4-yl)benzimidazole-4-carboxamide
54. 2-(N-methylpiperazin-4-yl)benzimidazole-4-carboxamide
55. 2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
56. 2-(N-isopropylpiperazin-4-yl)benzimidazole-4-carboxamide
57. 2-(N-cyclohexylpiperazin-4-yl)benzimidazole-4-carboxamide
58. 2-(N-(trans-4-propylcyclohex-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
59. 2-(N-benzylpiperazin-4-yl)benzimidazole-4-carboxamide
60. 2-(N-(2-phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
61. 2-(N-(2(4-fluorophenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
62. 2-(N-(2(4-chlorophenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
63. 2-(N-(2(4-bromophenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
64. 2-(N-(2(4-iodophenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
65. 2-(N-(2(4-nitrophenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
66. 2-(N-(2(4-cyanophenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
67. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
68. 2-(N-(2(4-methylphenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
69. 2-(N-(2(4-hydroxyphenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
70. 2-(N-(2(4-methoxyphenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
71. 2-(N-(2(4-(Nxe2x80x2,Nxe2x80x2-dimethylamino)phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
72. 2-(N-(2(4-(Nxe2x80x2-acetylamino)phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
73. 2-(N-(2(4-(Nxe2x80x2-phenylsulfonylamino)phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
74. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
75. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
76. 2-homopiperazin-4-ylbenzimidazole-4-carboxamide
77. 2-(N-acetylhomopiperazin-4-yl)benzimidazole-4-carboxamide
78. 2-(N(O-tert-butoxycarbonyl)homopiperazin-4-yl)benzimidazole-4-carboxamide
79. 2-(N-methylhomopiperazin-4-yl)benzimidazole-4-carboxamide
80. 2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
81. 2-(N-isopropylhomopiperazin-4-yl)benzimidazole-4-carboxamide
82. 2-(N-cyclohexylhomopiperazin-4-yl)benzimidazole-4-carboxamide
83. 2-(N-(trans-4-propylcyclohex-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
84. 2-(N-benzylhomopiperazin-4-yl)benzimidazole-4-carboxamide
85. 2-(N-(2-phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
86. 2-(N-(2(4-fluorophenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
87. 2-(N-(2(4-chlorophenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
88. 2-(N-(2(4-bromophenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
89. 2-(N-(2(4-iodophenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
90. 2-(N-(2(4-nitrophenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
91. 2-(N-(2(4-cyanophenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
92. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
93. 2-(N-(2(4-methylphenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
94. 2-(N-(2(4-hydroxyphenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
95. 2-(N-(2(4-methoxyphenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
96. 2-(N-(2(4-(Nxe2x80x2,Nxe2x80x2-dimethylamino)phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
97. 2-(N-(2(4-(Nxe2x80x2-acetylamino)phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
98. 2-(N-(2(4-(Nxe2x80x2-phenylsulfonylamino)phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
99. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
100. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
101. 1-methyl-2-(piperidin-4-yl)benzimidazole-4-carboxamide
102. 2-(N(O-tert-butoxycarbonyl)piperidin-4-yl)-1-methylbenzimidazole-4-carboxamide
103. 1-methyl-2-(N-methyl-piperidin-4-yl)benzimidazole-4-carboxamide
104. 1-methyl-2-(N-isopropyl-piperidin-4-yl)benzimidazole-4-carboxamide
105. 2-(N-benzylpiperidin-4-yl)-1-methylbenzimidazole-4-carboxamide
106. 1-methyl-2-(N-(2-phenyl)eth-1-yl)piperidin-4-yl)benzimidazole-4-carboxamide
107. 2-(N-(2(4-chlorophenyl)eth-1-yl)piperidin-4-yl)-1-methyl-benzimidazole-4-carboxamide
108. 2-(N-acetylpiperidin-3-yl)-1-methylbenzimidazole-4-carboxamide
109. 1-methyl-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
110. 2-(N-acetylpyrrolidin-3-yl)-1-methylbenzimidazole-4-carboxamide
111. 2-(N(O-tert-butoxycarbonyl)pyrrolidin-3-yl)-1-methyl-benzimidazole-4-carboxamide
112. 1-methyl-2-(N-methylpyrrolidin-3-yl)benzimidazole-4-carboxamide
113. 1-methyl-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
114. 1-methyl-2-(N-isopropylpyrrolidin-3-yl)benzimidazole-4-carboxamide
115. 2-(N-benzylpyrrolidin-3-yl)-1-methylbenzimidazole-4-carboxamide
116. 1-methyl-2-(N-(2-phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide
117. 2-(N-(2(4-chlorophenyl)eth-1-yl)pyrrolidin-3-yl)-1-methylbenzimidazole-4-carboxamide
118. 1-methyl-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
119. 2-(N-acetylpyrrolidin-2-yl)-1-methylbenzimidazole-4-carboxamide
120. 1-methyl-2-piperazin-4-ylbenzimidazole-4-carboxamide
121. 2-(N-acetylpiperazin-4-yl)-1-methylbenzimidazole-4-carboxamide
122. 2-(N(O-tert-butoxycarbonyl)piperazin-4-yl)-1-methyl-benzimidazole-4-carboxamide
123. 1-methyl-2-(N-methylpiperazin-4-yl)benzimidazole-4-carboxamide
124. 1-methyl-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
125. 1-methyl-2-(N-isopropylpiperazin-4-yl)benzimidazole-4-carboxamide
126. 2-(N-benzylpiperazin-4-yl)-1-methylbenzimidazole-4-carboxamide
127. 1-methyl-2-(N-(2-phenyl)eth-1-yl)piperazin-4-yl)benzimidazole-4-carboxamide
128. 2-(N-(2(4-chlorophenyl)eth-1-yl)piperazin-4-yl)-1-methyl-benzimidazole-4-carboxamide
129. 2-(homopiperazin-4-yl)-1-methylbenzimidazole-4-carboxamide
130. 2-(N-acetylhomopiperazin-4-yl)-1-methylbenzimidazole-4-carboxamide
131. 2-(N(O-tert-butoxycarbonyl)homopiperazin-4-yl)-1-methyl-benzimidazole-4-carboxamide
132. 1-methyl-2-(N-methylhomopiperazin-4-yl)benzimidazole-4-carboxamide
133. 1-methyl-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
134. 1-methyl-2-(N-isopropylhomopiperazin-4-yl)benzimidazole-4-carboxamide
135. 2-(N-benzylhomopiperazin-4-yl)-1-methylbenzimidazole-4-carboxamide
136. 1-methyl-2-(N-(2-phenyl)eth-1-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide
137. 2-(N-(2(4-chlorophenyl)eth-1-yl)homopiperazin-4-yl)-1-methyl-benzimidazole-4-carboxamide
138. 1-ethyl-2-(piperidin-4-yl)benzimidazole-4-carboxamide
139. 2-(piperidin-4-yl)-1-isopropylbenzimidazole-4-carboxamide
140. 1-(2-(hydroxy)eth-1-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide
141. 1-(2-(methoxy)eth-1-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide
142. 1-(2-(amino)eth-1-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide
143. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide
144. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide
145. 2-(piperidin-4-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
146. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide
147. 1-ethyl-2-(piperidin-3-yl)benzimidazole-4-carboxamide
148. 2-(piperidin-3-yl)-1-isopropylbenzimidazole-4-carboxamide
149. 1-(2-(hydroxy)eth-1-yl)-2-(piperidin-3-yl)benzimidazole-4-carboxamide
150. 1-(2-(methoxy)eth-1-yl)-2-(piperidin-3-yl)benzimidazole-4-carboxamide
151. 1-(2-(amino)eth-1-yl)-2-(piperidin-3-yl)benzimidazole-4-carboxamide
152. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(piperidin-3-yl)benzimidazol-4-carboxamide
153. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(piperidin-3-yl)benzimidazole-4-carboxamide
154. 2-(piperidin-3-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
155. 1-(2-(2-ethyl-piperidin-1-yl)eth-1-yl)-2-(piperidin-3-yl)benzimidazole-4-carboxamide
156. 1-ethyl-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
157. 1-isopropyl-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
158. 1-(2-(hydroxy)eth-1-yl)-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
159. 1-(2-(methoxy)eth-1-yl)-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
160. 1-(2-(amino)eth-1-yl)-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
161. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
162. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
163. 2-(pyrrolidin-3-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
164. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
165. 1-ethyl-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
166. 1-isopropyl-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
167. 1-(2-(hydroxy)eth-1-yl)-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
168. 1-(2-(methoxy)eth-1-yl)-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
169. 1-(2-(amino)eth-1-yl)-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
170. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
171. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
172. 2-(pyrrolidin-2-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
173. 1-(2-(2-ethyl-piperidin-1-yl)eth-1-yl)-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide
174. 1-ethyl-2-(piperazin-4-yl)benzimidazole-4-carboxamide
175. 1-isopropyl-2-(piperazin-4-yl)benzimidazole-4-carboxamide
176. 1-(2-(hydroxy)eth-1-yl)-2-(piperazin-4-yl)benzimidazole-4-carboxamide
177. 1-(2-(methoxy)eth-1-yl)-2-(piperazin-4-yl)benzimidazole-4-carboxamide
178. 1-(2-(amino)eth-1-yl)-2-(piperazin-4-yl)benzimidazole-4-carboxamide
179. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(piperazin-4-yl)benzimidazole-4-carboxamide
180. 2-(piperazin-4-yl)-1-(2-(piperidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
181. 2-(piperazin-4-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
182. 1-(2-(2-ethyl-piperidin-1-yl)eth-1-yl)-2-(piperazin-4-yl)benzimidazole-4-carboxamide
183. 1-ethyl-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
184. 1-isopropyl-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
185. 1-(2-(hydroxy)eth-1-yl)-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
186. 1-(2-(methoxy)eth-1-yl)-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
187. 1-(2-(amino)eth-1-yl)-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
188. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
189. 2-(homopiperazin-4-yl)-1-(2-(piperidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
190. 2-(homopiperazin-4-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
191. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
192. 1-ethyl-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
193. 1-isopropyl-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
194. 1-(2-(hydroxy)eth-1-yl)-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
195. 1-(2-(methoxy)eth-1-yl)-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
b 196. 1-(2-(amino)eth-1-yl)-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
197. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
198. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
199. 2-(N-propylpiperidin-4-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
200. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(N-propylpiperidin-4-yl)benzimidazole-4-carboxamide
201. 1-ethyl-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
202. 1-isopropyl-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
203. 1-(2-(hydroxy)eth-1-yl)-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
204. 1-(2-(methoxy)eth-1-yl)-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
205. 1-(2-(amino)eth-1-yl)-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
206. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
207. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
208. 2-(N-propylpiperidin-3-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
209. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(N-propylpiperidin-3-yl)benzimidazole-4-carboxamide
210. 1-ethyl-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
211. 1-isopropyl-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
212. 1-(2-(hydroxy)eth-1-yl)-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
213. 1-(2-(methoxy)eth-1-yl)-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
214. 1-(2-(amino)eth-1-yl)-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
215. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
216. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
217. 2-(N-propylpyrrolidin-3-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
218. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxamide
219. 1-ethyl-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
220. 1-isopropyl-2-(N-propyl-pyrrolidin-2-yl)benzimidazole-4-carboxamide
221. 1-(2-(hydroxy)eth-1-yl)-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
222. 1-(2-(methoxy)eth-1-yl)-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
223. 1-(2-(amino)eth-1-yl)-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
224. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
225. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
226. 2-(pyrrolidin-2-yl)-1-(2-(N-propylpyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
227. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(N-propylpyrrolidin-2-yl)benzimidazole-4-carboxamide
228. 1-ethyl-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
229. 1-isopropyl-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
230. 1-(2-(hydroxy)eth-1-yl)-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
231. 1-(2-(methoxy)eth-1-yl)-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
232. 1-(2-(amino)eth-1-yl)-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
233. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
234. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide
235. 2-(N-propyl-piperazin-4-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
236. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(N-propyl-piperazin-4-yl)benzimidazole-4-carboxamide
237. 1-ethyl-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
238. 1-isopropyl-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
239. 1-(2-(hydroxy)eth-1-yl)-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
240. 1-(2-(methoxy)eth-1-yl)-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
241. 1-(2-(amino)eth-1-yl)-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
242. 1-(2-(N,N-dimethylamino)eth-1-yl)-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
243. 1-(2-(piperidin-1-yl)eth-1-yl)-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
244. 2-(N-propylhomopiperazin-4-yl)-1-(2-(pyrrolidin-1-yl)eth-1-yl)benzimidazole-4-carboxamide
245. 1-(2-(2-ethylpiperidin-1-yl)eth-1-yl)-2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxamide
246. 6-chloro-2-(piperidin-4-yl)benzimidazole-4-carboxamide
247. 6-chloro-2-(piperidin-3-yl)benzimidazole-4-carboxamide
248. 6-chloro-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
249. 6-chloro-2-(piperazin-4-yl)benzimidazole-4-carboxamide
250. 6-chloro-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
251. 6-ethyl-2-(piperidin-4-yl)benzimidazole-4-carboxamide
252. 6-ethyl-2-(piperidin-3-yl)benzimidazole-4-carboxamide
253. 6-ethyl-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
254. 6-ethyl-2-(piperazin-4-yl)benzimidazole-4-carboxamide
255. 6-ethyl-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
256. 6-amino-2-(piperidin-4-yl)benzimidazole-4-carboxamide
257. 6-amino-2-(piperidin-3-yl)benzimidazole-4-carboxamide
258. 6-amino-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide
259. 6-amino-2-(piperazin-4-yl)benzimidazole-4-carboxamide
260. 6-amino-2-(homopiperazin-4-yl)benzimidazole-4-carboxamide
261. 2-(piperidin-4-yl)-6-(pyrrolidin-1-yl)benzimidazole-4-carboxamide
262. 2-(piperidin-3-yl)-6-(pyrrolidin-1-yl)benzimidazole-4-carboxamide
263. 2-(pyrrolidin-3-yl)-6-(pyrrolidin-1-yl)benzimidazole-4-carboxamide
264. 2-(piperazin-4-yl)-6-(pyrrolidin-1-yl)benzimidazole-4-carboxamide
265. 2-(homopiperazin-4-yl)-6-(pyrrolidin-1-yl)benzimidazole-4-carboxamide
266. 2-(3-methylpiperidin-4-yl)benzimidazole-4-carboxamide
267. 2-(3-cyclohexylpiperidin-4-yl)benzimidazole-4-carboxamide
268. 2-(2-cyclohexylpiperidin-4-yl)benzimidazole-4-carboxamide
269. 2-(3-phenylpiperidin-4-yl)benzimidazole-4-carboxamide
270. 2-(4-phenylpiperidin-4-yl)benzimidazole-4-carboxamide
271. 2-(2-(hydroxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide
272. 2-(2-(ethoxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide
273. 2-(2-(cyclohexyloxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide
274. 2-(2-(benoxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide
275. 2-(2-(phenoxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide